MEG3 in hematologic malignancies: from the role of disease biomarker to therapeutic target.

Maternally expressed gene 3 ( MEG3 ) is a noncoding RNA that is known as a tumor suppressor in solid cancers. Recently, a line of studies has emphasized its potential role in hematological malignancies in terms of tumorigenesis, metastasis, and drug resistance. Similar to solid cancers, MEG3 can regulate various cancer hallmarks via sponging miRNA, transcriptional, or posttranslational regulation mechanisms, but may regulate different key elements. In contrast with solid cancers, in some subtypes of leukemia, MEG3 has been found to be upregulated and oncogenic. In this review, we systematically describe the role and underlying mechanisms of MEG3 in multiple types of hematological malignancies. Particularly, we highlight the role of MEG3 in drug resistance and as a novel therapeutic target.

Effects of cadmium stress on the growth and physiological characteristics of sweet potato.

This study evaluated the responses of sweet potatoes to Cadmium (Cd) stress through pot experiments to theoretically substantiate their comprehensive applications in Cd-polluted agricultural land. The experiments included a CK treatment and three Cd stress treatments with 3, 30, and 150 mg/kg concentrations, respectively. We analyzed specified indicators of sweet potato at different growth periods, such as the individual plant growth, photosynthesis, antioxidant capacity, and carbohydrate Cd accumulation distribution. On this basis, the characteristics of the plant carbon metabolism in response to Cd stress throughout the growth cycle were explored. The results showed that T2 and T3 treatments inhibited the vine growth, leaf area expansion, stem diameter elongation, and tuberous root growth of sweet potato; notably, T3 treatment significantly increased the number of sweet potato branches. Under Cd stress, the synthesis of chlorophyll in sweet potato was significantly suppressed, and the Rubisco activity experienced significant reductions. With the increasing Cd concentration, the function of PS II was also affected. The soluble sugar content underwent no significant change in low Cd concentration treatments. In contrast, it decreased significantly under high Cd concentrations. Additionally, the tuberous root starch content decreased significantly with the increase in Cd concentration. Throughout the plant growth, the activity levels of catalase, peroxidase, and superoxide dismutase increased significantly in T2 and T3 treatments. By comparison, the superoxide dismutase activity in T1 treatment was significantly lower than that of CK. With the increasing application of Cd, its accumulation accordingly increased in various sweet potato organs. The the highest bioconcentration factor was detected in absorbing roots, while the tuberous roots had a lower bioconcentration factor and Cd accumulation. Moreover, the transfer factor from stem to petiole was the highest of the potato organs. These results demonstrated that sweet potatoes had a high Cd tolerance and a restoration potential for Cd-contaminated farmland.

Prognostic Implications of MRI-assessed Intratumoral Fat in Hepatocellular Carcinoma: An Asian and European Cohort Study.

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019). MRI scans were independently evaluated by three radiologists at each hospital. Based on Liver Imaging Reporting and Data System (LI-RADS) version 2018, intratumoral fat was defined as "fat in mass more than adjacent liver," and the homogeneous subtype was defined as intratumoral fat "in absence of mosaic and nodule-in-nodule architecture." Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analyses were conducted to identify factors associated with RFS and OS. Results A total of 933 patients were included in the Asian (n = 736; median age, 53 years [IQR, 45-62 years]; 626 male) and European (n = 207; median age, 64 years [IQR, 55-70 years]; 161 male) cohorts. MRI-assessed intratumoral fat was detected in 30% (215 of 726) and 31% (64 of 207) of patients in the Asian and European cohorts, respectively (P = .72). In both cohorts, the steatohepatitic subtype, nonperipheral washout, enhancing capsule, and mosaic architecture were more frequent in tumors with intratumoral fat (P value range, <.001 to .04). Intratumoral fat in general was not associated with RFS or OS in either cohort (P value range, .48-.97). However, in the Asian cohort, homogeneous intratumoral fat was associated with longer RFS (hazard ratio [HR], 0.60; P = .009) and OS (HR, 0.33; P = .008) in multivariable Cox regression analyses. Conclusion MRI-assessed intratumoral fat was more frequent in steatohepatitic HCCs and associated with nonperipheral washout, enhancing capsule, and mosaic architecture. Although intratumoral fat was generally nonprognostic, homogeneous intratumoral fat was associated with longer RFS and OS in the Asian cohort. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Harmath in this issue.

MRI-based prediction of the need for wide resection margins in patients with single hepatocellular carcinoma.

OBJECTIVES: To develop an MRI-based score that enables individualized predictions of the survival benefit of wide over narrow resection margins. MATERIALS AND METHODS: This single-center retrospective study (December 2011 to May 2022) included consecutive patients who underwent curative-intent resection for single Barcelona Clinic Liver Cancer (BCLC) 0/A HCC and preoperative contrast-enhanced MRI. In patients with narrow resection margins, preoperative demographic, laboratory, and MRI variables independently associated with early recurrence-free survival (RFS) were identified using Cox regression analyses, which were employed to develop a predictive score (named "MARGIN"). Survival outcomes were compared between wide and narrow resection margins in a propensity-score matched cohort for the score-stratified low- and high-risk groups, respectively. RESULTS: Four hundred nineteen patients (median age, 54 years; 361 men) were included, 282 (67.3%) undergoing narrow resection margins. In patients with narrow resection margins, age, alpha-fetoprotein (AFP) > 400 ng/mL, protein induced by vitamin K absence or antagonist-II (PIVKA-II) > 200 mAU/mL, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS (p values, 0.002-0.04) and formed the MARGIN score with a testing dataset C-index of 0.75 (95% CI: 0.65-0.84). In the matched cohort, wide resection margin was associated with improved early RFS rate for the high-risk group (MARGIN score ≥ - 1.3; 71.1% vs 41.0%; p = 0.02), but not for the low-risk group (MARGIN score < - 1.3; 79.7% vs 76.1%; p = 0.36). CONCLUSION: In patients with single BCLC 0/A HCC, the MARGIN score may serve as promising decision-making to indicate the need for wide resection margins. CLINICAL RELEVANCE STATEMENT: The MARGIN score has the potential to identify patients who would benefit more from wide resection margins than narrow resection margins, improving the postoperative survival of patients with single BCLC 0/A hepatocellular carcinoma (HCC). KEY POINTS: Age, AFP, PIVKA-II, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS and formed the MARGIN score. The MARGIN score achieved a testing dataset C-index of 0.75. Wide resection margins were associated with improved early RFS for the high-risk group, but not for the low-risk group.

Curative Effect of Bracketless and Invisible Orthodontic Treatment for Periodontitis and the Influence on Gingival Crevicular Fluid and Serum IL-6, MMP-8 and TNF-α Levels.

Objective: To observe the therapeutic effects of bracketless and invisible orthodontic treatment on periodontitis, as well as on gingival crevicular fluid and serum interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and tumors. The impact of necrosis factor-alpha (TNF-α) levels fills the current knowledge gap regarding the impact of different orthodontic treatment modalities on biomarker levels in periodontitis patients. Methods: 100 patients with malocclusion secondary to periodontitis were selected as subjects.They were divided into a control group (n=50) and a study group (n=50) according to the random number method. The control group was treated with a straight wire appliances, and the study group was given bracketless and invisible orthodontic treatment. Clinical effects, Periodontal indicators [plaque index (PLI), gingival crevicular bleeding index (SBI), gingival index (GI), periodontal pocket probe depth (PD), clinical attachment loss (CAL)], gingival crevicular fluid and serum IL-6, MMP-8 and TNF-α levels and the incidence of adverse reactions were compared between the two groups. The uniqueness of this method is that it compares the impact of traditional straight-wire orthodontic treatment and invisible orthodontic treatment without brackets on biomarker levels and clinical effects in patients with periodontitis. In order to understand the role of orthodontic treatment methods in Provides useful information for use in periodontitis treatment. Results: The main findings of this study highlight the significant impact of bracketless clear braces in improving periodontal indicators and cytokine levels. Patients treated with bracketless clear braces demonstrate better clinical outcomes in periodontitis treatment compared with traditional straight-wire orthodontic treatment. The response rate of the study group was higher than that of the control group (94.00% vs. 72.00%) (P < .05). After 2 years of treatment, PLT, SBI, GI, PD and CAL were decreased in both groups and the observation group was significantly lower than the control group (P < .05). After 6 months of treatment, the levels of IL-6, MMP-8 and TNF-α in gingival crevicular fluid and serum were decreased in both groups, and the observation group was significantly lower than the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the two groups (P > .05). Conclusion: The treatment of periodontitis without brackets has a significant effect, which can improve the periodontal condition and reduce the levels of IL-6, MMP-8 and TNF-α in gingival crevicular fluid and serum. Bracketless invisible braces have shown potential clinical significance in improving periodontal indicators and cytokine levels in patients with periodontitis, providing support for providing more comfortable and effective orthodontic treatment options, which may help promote patients' Oral health. These findings suggest the positive role of bracketless invisible braces in comprehensive periodontal treatment, which is expected to influence the practice of orthodontics and periodontal treatment and improve patient treatment experience and effects.

Clinical Decision Support System Used in Spinal Disorders: Scoping Review.

BACKGROUND: Spinal disorders are highly prevalent worldwide with high socioeconomic costs. This cost is associated with the demand for treatment and productivity loss, prompting the exploration of technologies to improve patient outcomes. Clinical decision support systems (CDSSs) are computerized systems that are increasingly used to facilitate safe and efficient health care. Their applications range in depth and can be found across health care specialties. OBJECTIVE: This scoping review aims to explore the use of CDSSs in patients with spinal disorders. METHODS: We used the Joanna Briggs Institute methodological guidance for this scoping review and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. Databases, including PubMed, Embase, Cochrane, CINAHL, Web of Science, Scopus, ProQuest, and PsycINFO, were searched from inception until October 11, 2022. The included studies examined the use of digitalized CDSSs in patients with spinal disorders. RESULTS: A total of 4 major CDSS functions were identified from 31 studies: preventing unnecessary imaging (n=8, 26%), aiding diagnosis (n=6, 19%), aiding prognosis (n=11, 35%), and recommending treatment options (n=6, 20%). Most studies used the knowledge-based system. Logistic regression was the most commonly used method, followed by decision tree algorithms. The use of CDSSs to aid in the management of spinal disorders was generally accepted over the threat to physicians' clinical decision-making autonomy. CONCLUSIONS: Although the effectiveness was frequently evaluated by examining the agreement between the decisions made by the CDSSs and the health care providers, comparing the CDSS recommendations with actual clinical outcomes would be preferable. In addition, future studies on CDSS development should focus on system integration, considering end user's needs and preferences, and external validation and impact studies to assess effectiveness and generalizability. TRIAL REGISTRATION: OSF Registries osf.io/dyz3f; https://osf.io/dyz3f.

A new cytotoxic disaccharide glycoside from the tubers of Arisaema franchetianum.

A new disaccharide glycoside, franchoside A (1), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 2, 6, 10, 14 and 18 showed significant cytotoxic activities at varying IC50 values in the range of 4.0-10.6 µM against five cancer cell lines. Compounds 8, 10, 13 and 17 (10 µM) exhibited moderate anti-inflammatory activities by inhibiting the NF-κB signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1, 9, 14, 15 and 16 showed weak anti-inflammatory activities.

VICT2 Trait: Prognostic Alternative to Peritumoral Hepatobiliary Phase Hypointensity in HCC.

Background Peritumoral hepatobiliary phase (HBP) hypointensity is an established prognostic imaging feature in hepatocellular carcinoma (HCC), often associated with microvascular invasion (MVI). Similar prognostic features are needed for non-HBP MRI. Purpose To propose a non-hepatobiliary-specific MRI tool with similar prognostic value to peritumoral HBP hypointensity. Materials and Methods From December 2011 to November 2021, consecutive patients with HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled and followed up until recurrence. All MRI scans were reviewed by two blinded radiologists with 7 and 10 years of experiences with liver MRI. A scoring system based on non-hepatobiliary-specific features that highly correlated with peritumoral HBP hypointensity was identified in a stratified sampling-derived training set of the gadoxetate disodium (EOB) group by means of multivariable logistic regression, and its values to predict MVI and recurrence-free survival (RFS) were assessed. Results There were 660 patients (551 men; median age, 53 years; IQR, 45-61 years) enrolled. Peritumoral portal venous phase hypoenhancement (odds ratio [OR] = 8.8), incomplete "capsule" (OR = 3.3), corona enhancement (OR, 2.6), and peritumoral mild-moderate T2 hyperintensity (OR, 2.2) (all P < .001) were associated with peritumoral HBP hypointensity and constituted the "VICT2 trait" (test set area under the receiver operating characteristic curve = 0.84; 95% CI: 0.78, 0.90). For the EOB group, both peritumoral HBP hypointensity (OR for MVI = 2.5, P = .02; hazard ratio for RFS = 2.5, P < .001) and the VICT2 trait (OR for MVI = 5.1, P < .001; hazard ratio for RFS = 2.3, P < .001) were associated with MVI and RFS, despite a higher specificity of the VICT2 trait for MVI (89% vs 80%, P = .01). These values of the VICT2 trait were confirmed in the extracellular contrast agent group (OR for MVI = 4.0; hazard ratio for RFS = 1.7; both P < .001). Conclusion Based on four non-hepatobiliary-specific MRI features, the VICT2 trait was comparable to peritumoral hepatobiliary phase hypointensity in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Unbalance between working memory task-activation and task-deactivation networks in epilepsy: Simultaneous EEG-fMRI study.

Working memory (WM) is a cognitive function involving emergent properties of theta oscillations and large-scale network interactions. The synchronization of WM task-related networks in the brain enhanced WM performance. However, how these networks regulate WM processing is not well known, and the alteration of the interaction among these networks may play an important role in patients with cognitive dysfunction. In this study, we used simultaneous EEG-fMRI to examine the features of theta oscillations and the functional interactions among activation/deactivation networks during the n-back WM task in patients with idiopathic generalized epilepsy (IGE). The results showed that there was more enhancement of frontal theta power along with WM load increase in IGE, and the theta power was positively correlated with the accuracy of the WM tasks. Moreover, fMRI activations/deactivations correlated with n-back tasks were estimated, and we found that the IGE group had increased and widespread activations in high-load WM tasks, including the frontoparietal activation network and task-related deactivation areas, such as the default mode network and primary visual and auditory networks. In addition, the network connectivity results demonstrated decreased counteraction between the activation network and deactivation network, and the counteraction was correlated with the higher theta power in IGE. These results indicated the important role of the interactions between activation and deactivation networks during the WM process, and the unbalance among them may indicate the pathophysiological mechanism of cognitive dysfunction in generalized epilepsy.

Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study.

BACKGROUND AIMS: The RELIANCE study has demonstrated the activity and safety of relmacabtagene autoleucel (relma-cel) (JW Therapeutics [Shanghai] Co, Ltd, Shanghai, China), a CD19-targeted chimeric antigen receptor T-cell product, in patients with heavily pre-treated relapsed/refractory large B-cell lymphoma (r/r LBCL). This study aimed to report the updated 2-year data of the RELIANCE study. METHODS: The RELIANCE study (NCT04089215) was an open-label, multi-center, randomized, phase 1/2 registrational clinical trial conducted at 10 clinical sites in China. Adult patients with heavily pre-treated r/r LBCL were enrolled and received lymphodepletion chemotherapy followed by infusion of 100 × 106 or 150 × 106 relma-cel. The primary endpoint was objective response rate (ORR) at 3 months, as assessed by investigators. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety profiles. RESULTS: From November 2017 to January 2022, a total of 68 patients were enrolled, and 59 patients received relma-cel infusion. As of March 29, 2022, a total of 59 patients had a median follow-up of 17.9 months (range, 0.3-25.6). ORR was 77.59% (95% confidence interval [CI], 64.73-87.49) and complete response rate was 53.45% (95% CI, 39.87-66.66). Median DoR was 20.3 months (95% CI, 4.86-not reached [NR]) and median PFS was 7.0 months (95% CI, 4.76-24.15). Median OS was NR and 1-year and 2-year OS rates were 75.0% and 69.3%, respectively. Three (5.1%) patients experienced grade ≥3 cytokine release syndrome and two (3.4%) patients had grade ≥3 neurotoxicity. CONCLUSIONS: The updated data of the RELIANCE study demonstrate durable response with and manageable safety profile of relma-cel in patients with heavily pre-treated r/r LBCL.

Development and validation of the OSASH score to predict overall survival of hepatocellular carcinoma after surgical resection: a dual-institutional study.

OBJECTIVE: To develop and validate a risk score based on preoperative clinical-radiological parameters for predicting overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma (HCC). METHODS: From July 2010 to December 2021, consecutive patients with surgically-proven HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled. A preoperative OS risk score was constructed in the training cohort using a Cox regression model and validated in a propensity score-matched internal validation cohort and an external validation cohort. RESULTS: A total of 520 patients were enrolled, among whom 210, 210, and 100 patients were from the training, internal validation, and external validation cohorts, respectively. Independent predictors for OS included incomplete tumor "capsule," mosaic architecture, tumor multiplicity, and serum alpha-fetoprotein, which were incorporated into the "OSASH score." The C-index the OSASH score was 0.85, 0.81, and 0.62 in the training, internal, and external validation cohorts, respectively. Using 32 as the cutoff point, the OSASH score stratified patients into prognostically distinct low- and high-risk groups among all study cohorts and six subgroups (all p < 0.05). Furthermore, patients with BCLC stage B-C HCC and OSASH-low risk achieved comparable OS to that of patients with BCLC stage 0-A HCC and OSASH-high risk in the internal validation cohort (5-year OS rates, 74.7 vs. 77.8%; p = 0.964). CONCLUSION: The OSASH score may help predict OS in HCC patients undergoing hepatectomy and identify potential surgical candidates among those with BCLC stage B-C HCC. CLINICAL RELEVANCE STATEMENT: By incorporating three preoperative MRI features and serum AFP, the OSASH score may help predict postsurgical overall survival in patients with hepatocellular carcinoma and identify potential surgical candidates among those with BCLC stage B and C HCC. KEY POINTS: • The OSASH score incorporating three MRI features and serum AFP can be used to predict OS in HCC patients who received curative-intent hepatectomy. • The score stratified patients into prognostically distinct low- and high-risk strata in all study cohorts and six subgroups. • Among patients with BCLC stage B and C HCC, the score identified a subgroup of low-risk patients who achieved favorable outcomes after surgery.

Prognostic MRI features to predict postresection survivals for very early to intermediate stage hepatocellular carcinoma.

OBJECTIVES: Contrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS). MATERIALS AND METHODS: Consecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS. RESULTS: This study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p = .02). Nonperipheral washout (p = .006), markedly low apparent diffusion coefficient value (p = .02), intratumoral arteries (p = .01), and width of the main portal vein (p = .03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p = .02). Multiple tumors (p = .048) and radiologically-evident cirrhosis (p < .001) were the only predictors for L-RFS. CONCLUSION: Twelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs. CLINICAL RELEVANCE STATEMENT: The prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models. KEY POINTS: • Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival. • Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival. • Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years.

Genomic evolution and diverse models of systemic metastases in colorectal cancer.

OBJECTIVE: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. DESIGN: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. RESULTS: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. CONCLUSION: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.

Modifying LI-RADS on Gadoxetate Disodium-Enhanced MRI: A Secondary Analysis of a Prospective Observational Study.

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is widely used for diagnosing hepatocellular carcinoma (HCC), however, with unsatisfactory sensitivity, complex ancillary features, and inadequate integration with gadoxetate disodium (EOB)-enhanced MRI. PURPOSE: To modify LI-RADS (mLI-RADS) on EOB-MRI. STUDY TYPE: Secondary analysis of a prospective observational study. POPULATION: Between July 2015 and September 2018, 224 consecutive high-risk patients (median age, 51 years; range, 26-83; 180 men; training/testing sets: 169/55 patients) with 742 (median size, 13 mm; interquartile range, 7-27; 498 HCCs) LR-3/4/5 observations. FIELD STRENGTH/SEQUENCE: 3.0 T T2 -weighted fast spin-echo, diffusion-weighted spin-echo based echo-planar, and 3D T1 -weighted gradient echo sequences. ASSESSMENT: Three radiologists (with 5, 5, and 10 years of experience in liver MR imaging, respectively) blinded to the reference standard (histopathology or imaging follow-up) reviewed all MR images independently. In the training set, the optimal LI-RADS version 2018 (v2018) features selected by Random Forest analysis were used to develop mLI-RADS via decision tree analysis. STATISTICAL TESTS: In an independent testing set, diagnostic performances of mLI-RADS, LI-RADS v2018, and the Korean Liver Cancer Association (KLCA) guidelines were computed using a generalized estimating equation model and compared with McNemar's test. A two-tailed P < 0.05 was statistically significant. RESULTS: Five features (nonperipheral "washout," restricted diffusion, nonrim arterial phase hyperenhancement [APHE], mild-moderate T2 hyperintensity, and transitional phase hypointensity) constituted mLI-RADS, and mLR-5 was nonperipheral washout coupled with either nonrim APHE or restricted diffusion. In the testing set, mLI-RADS was significantly more sensitive (72%) and accurate (80%) than LI-RADS v2018 (sensitivity, 61%; accuracy 74%; both P < 0.001) and the KLCA guidelines (sensitivity, 64%; accuracy 74%; both P < 0.001), without sacrificing positive predictive value (mLI-RADS, 94%; LI-RADS v2018, 94%; KLCA guidelines, 92%). DATA CONCLUSION: In high-risk patients, the EOB-MRI-based mLI-RADS was simpler and more sensitive for HCC than LI-RADS v2018 while maintaining high positive predictive value. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Data-Driven Modification of the LI-RADS Major Feature System on Gadoxetate Disodium-Enhanced MRI: Toward Better Sensitivity and Simplicity.

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is widely accepted as a reliable diagnostic scheme for hepatocellular carcinoma (HCC) in at-risk patients. However, its application is hampered by substantial complexity and suboptimal diagnostic sensitivity. PURPOSE: To propose data-driven modifications to the LI-RADS version 2018 (v2018) major feature system (rLI-RADS) on gadoxetate disodium (EOB)-enhanced magnetic resonance imaging (MRI) to improve sensitivity and simplicity while maintaining high positive predictive value (PPV) for detecting HCC. STUDY TYPE: Retrospective. POPULATION: Two hundred and twenty-four consecutive at-risk patients (training dataset: 169, independent testing dataset: 55) with 742 LR-3 to LR-5 liver observations (HCC: N = 498 [67%]) were analyzed from a prospective observational registry collected between July 2015 and September 2018. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted fast spin-echo, diffusion-weighted spin-echo based echo-planar and three-dimensional (3D) T1-weighted gradient echo sequences. ASSESSMENT: All images were evaluated by three independent abdominal radiologists who were blinded to all clinical, pathological, and follow-up information. Composite reference standards of either histopathology or imaging follow-up were used. STATISTICAL TESTS: In the training dataset, LI-RADS v2018 major features were used to develop rLI-RADS based on their associated PPV for HCC. In an independent testing set, diagnostic performances of LI-RADS v2018 and rLI-RADS were computed using a generalized estimating equation model and compared with McNemar's test. A P value <0.05 was considered statistically significant. RESULTS: The median (interquartile range) size of liver observations was 13 mm (7-27 mm). The diagnostic table for rLI-RADS encompassed 9 cells, as opposed to 16 cells for LI-RADS v2018. In the testing set, compared to LI-RADS v2018, rLI-RADS category 5 demonstrated a significantly superior sensitivity (76% vs. 61%) while maintaining comparably high PPV (92.5% vs. 94.1%, P = 0.126). DATA CONCLUSION: Compared with LI-RADS v2018, rLI-RADS demonstrated improved simplicity and significantly superior diagnostic sensitivity for HCC in at-risk patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Predicting microvascular invasion in hepatocellular carcinoma: A dual-institution study on gadoxetate disodium-enhanced MRI.

BACKGROUND & AIMS: Microvascular invasion (MVI) is an important risk factor in hepatocellular carcinoma (HCC), but its diagnosis mandates postoperative histopathologic analysis. We aimed to develop and externally validate a predictive scoring system for MVI. METHODS: From July 2015 to November 2020, consecutive patients underwent surgery for HCC with preoperative gadoxetate disodium (EOB)-enhanced MRI was retrospectively enrolled. All MR images were reviewed independently by two radiologists who were blinded to the outcomes. In the training centre, a radio-clinical MVI score was developed via logistic regression analysis against pathology. In the testing centre, areas under the receiver operating curve (AUCs) of the MVI score and other previous MVI schemes were compared. Overall survival (OS) and recurrence-free survival (RFS) were analysed by the Kaplan-Meier method with the log-rank test. RESULTS: A total of 417 patients were included, 195 (47%) with pathologically-confirmed MVI. The MVI score included: non-smooth tumour margin (odds ratio [OR] = 4.4), marked diffusion restriction (OR = 3.0), internal artery (OR = 3.0), hepatobiliary phase peritumoral hypointensity (OR = 2.5), tumour multifocality (OR = 1.6), and serum alpha-fetoprotein >400 ng/mL (OR = 2.5). AUCs for the MVI score were 0.879 (training) and 0.800 (testing), significantly higher than those for other MVI schemes (testing AUCs: 0.648-0.684). Patients with model-predicted MVI had significantly shorter OS (median 61.0 months vs not reached, P < .001) and RFS (median 13.0 months vs. 42.0 months, P < .001) than those without. CONCLUSIONS: A preoperative MVI score integrating five EOB-MRI features and serum alpha-fetoprotein level could accurately predict MVI and postoperative survival in HCC. Therefore, this score may aid in individualized treatment decision making.

Comparison of a preoperative MR-based recurrence risk score versus the postoperative score and four clinical staging systems in hepatocellular carcinoma: a retrospective cohort study.

OBJECTIVES: To establish a risk score integrating preoperative gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and clinical parameters to predict recurrence after hepatectomy for patients with hepatocellular carcinoma (HCC) and to compare its performance with that of a postoperative score and four clinical staging systems. METHODS: Consecutive patients with surgically confirmed HCC who underwent preoperative EOB-MRI between July 2015 and November 2020 were retrospectively included. Two recurrence risk scores, one incorporating only preoperative variables and the other incorporating all preoperative and postoperative variables, were constructed via Cox regression models. RESULTS: A total of 214 patients (derivation set, n = 150; test set, n = 64) were included. Six preoperative variables, namely tumor number, infiltrative appearance, corona enhancement, alpha-fetoprotein (AFP) level, aspartate aminotransferase (AST) level, and sex, were independently associated with recurrence. After adding postoperative features, microvascular invasion and tumor differentiation were additional significant variables in lieu of corona enhancement and AFP level. Using the above variables, the preoperative score achieved a C-index of 0.741 on the test set, which was comparable with that of the postoperative score (0.729; p = 0.235). The preoperative score yielded a larger time-dependent area under the receiver operating characteristic curve at 1 year (0.844) than three existing systems (0.734-0.742; p < 0.05 for all). Furthermore, the preoperative score stratified patients into two prognostically distinct risk strata with low and high risks of recurrence (p < 0.001). CONCLUSION: The preoperative score integrating EOB-MRI features, AFP and AST levels, and sex improves recurrence risk estimation in HCC. KEY POINTS: • The preoperative risk score incorporating three EOB-MRI findings, AFP and AST levels, and sex achieved comparable performance with that of the postoperative score for predicting recurrence after hepatectomy in patients with HCC. • Two risk strata with low and high risks of recurrence were obtained based on the preoperative score. • The preoperative score may help tailor pretreatment decision-making and facilitate candidate selection for adjuvant clinical trials.

Underwater endoscopic mucosal resection for rectal neuroendocrine tumors (with videos): a single center retrospective study.

BACKGROUND: Underwater endoscopic mucosal resection (UMER) is a new method of endoscopic resection to completely remove the lesion without submucosal injection. But few attempts have been carried out for rectal neuroendocrine tumors (rectal NETs). METHODS: We retrospectively investigated data on the tumor characteristics and outcomes of patients with ≤ 10 mm rectal NETs who underwent UEMR or endoscopic submucosal dissection (ESD) from January 2019 to June 2021 in our institute. RESULTS: The endoscopic resection rate was 100% in both UEMR and ESD groups. The histological complete resection rate of the UEMR group (95.5%) was lower than that of the ESD group (96.4%) with no significant difference. The average operation time, hospitalization time and operation cost of UEMR group were less than those of ESD group (P < 0.05). The incidence of postoperative abdominal pain and abdominal distention in the UEMR group was lower than that in the ESD group (P < 0.05). There was no significant difference in the incidence of delayed bleeding and perforation between the two groups. There was no local recurrence or distant metastasis in the two groups during the follow-up period. CONCLUSIONS: Both the UEMR and ESD can effectively treat ≤ 10 mm rectal NETs with invasion depth confined to the mucosa and submucosa. UEMR is superior to ESD in operation time, hospitalization time, operation cost, postoperative abdominal pain and abdominal distention.

Probing the Functional and Structural Connectivity Underlying EEG Traveling Waves.

Neural oscillations play an important role in the maintenance of brain function by regulating multi-scale neural activity. Characterizing the traveling properties of EEG is helpful for understanding the spatiotemporal dynamics of neural oscillations. However, traveling EEG based on non-invasive approach has little been investigated, and the relationship with brain intrinsic connectivity is not well known. In this study, traveling EEG of different frequency bands on the scalp in terms of the center of mass (EEG-CM) was examined. Then, two quantitative indexes describing the spatiotemporal features of EEG-CM were proposed, i.e., the traveling lateralization and velocity of EEG-CM. Further, based on simultaneous EEG-MRI approach, the relationship between traveling EEG-CM and the resting-state functional networks, as well as the microstructural connectivity of white matter was investigated. The results showed that there was similar spatial distribution of EEG-CM under different frequency bands, while the velocity of rhythmic EEG-CM increased in higher frequency bands. The lateralization of EEG-CM in low frequency bands (< 30 Hz) demonstrated negative relationship with the basal ganglia network (BGN). In addition, the velocity of the traveling EEG-CM was associated with the fractional anisotropy (FA) in corpus callosum and corona radiate. These results provided valid quantitative EEG index for understanding the spatiotemporal characteristics of the scalp EEG, and implied that the EEG dynamics were representations of functional and structural organization of cortical and subcortical structures.

Psychological impacts and online interventions of social isolation amongst older adults during COVID-19 pandemic: A scoping review.

AIM: To summarise the psychological impacts of social isolation amongst older adults during COVID-19 and review the benefits and limitations of online interventions used to combat social isolation. DESIGN: A scoping review was performed. DATA SOURCES: A systematic search was performed from October 2020 to January 2021 in seven electronic databases: China National Knowledge Infrastructure (CNKI), PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Cochrane Library and Web of Science. A hand search of the reference lists of included papers and WHO publications was performed. Grey literature search was carried out from Scopus, ProQuest Dissertation and Google Scholar. REVIEW METHODS: Studies were screened, appraised and extracted independently by two reviewers. Thematic analysis was used to synthesise data, which were presented in a descriptive manner and organised into categories and themes. RESULTS: Totally, 33 studies were included. Four themes and eight sub-themes emerged: (1) negative impacts and experiences of older adults during social isolation, (2) adopting coping behaviours in the midst of COVID-19, (3) online interventions to combat the consequences of social isolation, (4) barriers to online intervention. CONCLUSION: The COVID-19 pandemic has taken an emotional toll on older adults' psychological wellbeing and has highlighted the untapped strengths of older adults facing isolation. Online interventions, which could be a new normal in the COVID era, were beneficial in combating social isolation. Strategies by various stakeholders were recommended to tackle the barriers of online interventions. IMPACT: With the COVID-19 pandemic still in progress, this review provides insights on the psychological impacts of social isolation amongst older adults. Nurses in the community and long-term care facilities could adopt strategies and online intervention to better support the older adults, contribute to a stronger COVID-19 response and support system, and an overall better road to recovery from this crisis.